EXCEED THE SPACE PROVIDED. This is a proposal to renew the NCRR COBRE Center for Protein Structure and Function at the University of Arkansas, which was established in October, 2000 with NIH COBRE Grant 1 P20 RR15569-01. Protein structure and function is a central biomedical research area that has great potential for leading to improvements in human health. The goals of the COBRE Center are to strengthen collaboration between investigators and allow them to develop promising new approaches to biomedical research in protein structure and function. The Center is building upon the unique research expertise of our faculty in the areas of X-ray crystallography, NMR spectroscopy, mass spectrometry, and drug discovery. The center will support five thematically-linked multidisciplinary research projects involving 8 junior faculty and 5 newfaculty who receive direct NIH COBRE grant support, and 8 senior faculty who provide expertise in a broad range of techniques needed to study protein structure and function. The Center provides the junior investigators with the support and mentoring necessary to develop nationally competitive biomedical research careers. All five research projects will involve a multidisciplinary, collaborative approach to obtaining a better understanding of the structure and function of biomedically important proteins. Project 1will focus on the interaction of the human fibroblast growth factor protein with its receptor, which regulates a wide array of key physiological processes including embryogenesis, cell growth, differentiation, and wound healing. Project 2 will explore new approaches to determining the structures of signal recognition particles, which facilitate protein targeting. Project 3 will involve a study of proteins of the extracellular matrix, including collagen binding proteins. Project 4 will involve the development of new families of specific protein inhibitors as candidates for new drugs. Project 5 will focus on studies of the structure and function of membrane proteins. All of the projects are focused on problems that could lead to improvements in human health. For example, project 1 could lead to new therapeutic strategies against a variety of fibroblast growth factor-mediated disorders and wound healing, project 3 is directed towards development of a novel drug-delivery vehicle for the extracellular matrix which could lead to improved nerve regeneration, and project 4 is focused on the development of improved Pharmaceuticals to treat Hepatitis C and HIV.